Pharmacokinetics and drug related problems in geriatric

(Farmakokinetik dan obat terkait masalah geriatri)

Geriatric patients
Overview problems
Increased risk when they receive medications. 39 % of all hospitalization and 51 % of death from drug reactions. Taking multiple medications as particular problems Mismedications : prescription of higher dosages than needed for adequate effects, prescription of more dangerous drug when less toxic preparation would be equally effective, prescription of drugs that are unnecessary, use of drug combinations that produce adverse effects. Problems with compliance : poor vision and hearing, decline in cognitive function, use of complicated drug regimens with large numbers of medications, difficulty opening chlidproof containers.

Factors affecting drug disposition in the geriatric patient

Kinetic parameters Absorption Age-related physiologic change Gastric pH Absorptive surface Splanchnic BF GI motility Pathologic condition Therapeutic & environ. factors Achlorhydria Diarrhea Postgastrectomy Pancreatitis Antacids Anticholinergics Cholestyramine Food & meals

Distribution

Cardiac output
Total body water

CHF
Dehydration

Drug interaction
Protein binding deplacement

Lean body mass

Serum albumin Proportion body fat Metabolism Hepatic mass Hepatic blood flow Excretion Renal BF GFR Tubular secretion

Edema
Hepatic failure Malnutrition CHF, malnutrition Fever, malignancy Hypovolemia Renal insufficiency

Dietary composition Drug interaction Drug interaction

Altered pharmacokinetics in the elderly (Perubahan farmakokinetik pada lansia)

Most drugs released to marketing have their pharmacokinetics investigated in younger volunteers or patients. Aged-related changes in drug pharmacokinetics are complex and often difficult to predict. Hepatic function reduce the first pass effect oral bioavailability. Total body water & total body fat & albumin plasma alteration in the Vd of some drugs. Blood flow to the liver and kidney drug clearance Change in drug distribution and drug clearance may combine to cause large changes in elimination hal life for certain drugs.

Drug with decreased renal elimination in old age

N-acetylprocainamide Amantadine Amikacin Ampicillin Atenolol Cefriaxone Cephradine Chlorpropamide Cimetidine Digoxin Doxycycline Furosemide Gentamicin HCT Lithium Pancuronium Phenobarbital Procainamide Ranitidine Satolol Sulfamethiazole Tetracycline Tobramycin Triamteren

Cibenzoline

Penicillin

Theophyline

Clcreat (ml/min) =

(140 age) x weight (kg) 72 x Cp, creat (mg/dl)

Adverse drug reactions and drug interactions

The elderly experience an excessive number of ADR & drug interaction. Age itself may not be an independent risk factor. The presence of more diseases, more severe disease, altered pharmacodynamics and more justified medications all act together increase the probability of an ADR. Some ADR may often be unavoidable without also avoiding efficacy. Example : elderly are more likely to received both digoxin & quinidin Css of digoxin . Certain drug may have such excessive risk profile when given to the elderly. Example : Amitriptyline excessive anticholinergic effects; chlorpropamide prolonged hypoglycemia.

Change in organs function Plasma conc. Respons Homeostasis

Adverse drug reactions

Multy diseases

Polypharmacy

Compliance

Factors increasing in ADR in the elderly

Important drug-disease interactions in geriatric patients

Underlying disease
Dementia Galucoma Congestive heart failure Cardiac conduction disorders Hypertension Chronic obstructive pulmonary disease Chronic renal impairment Diabetes mellitus Hypokalemia Peptic ulcer disease

Drug
Psychotropic, antiepileptic Antimuscarinic -blocker, verapamil Tricyclic antidepressants NSAID -blocker Opioid agents NSAID, aminoglycosides Diuretics, prednisone Digoxin NSAID, anticoagulants

Adverse effect
Convulsion, delirium Acute glucoma Acute cardiac decom. Heart block Blood pressure Bronchoconstriction Respiratory depression Acute renal failure Hyperglycemia Cardiac arrhythmias Gastrointestinal hemorrhage

Principles geriatric prescribing

Evaluate the need for drug therapy Not all disease required drug treatment Avoid drug if possible, but not withhold because of age drugs that might enhance quality of life Strive for diagnosis before treatment Take careful history of habits and drug use Patients often seek advice and received prescriptions from several physicians Knowledge of existing therapy, both prescribed and non prescribed, help anticipate potential drug interaction Smoking, alcohol, and caffeine may effect drug response and need to be taken in account Know the pharmacology of the drug prescribed Use few drug well Awareness of age-related alterations in drug disposition and drug response is helpful In general, begin therapy with relatively small dose The standard dose often too large for elderly patients Renal excretion of drugs and active metabolites tends to decline Sensitive to drugs affecting CNS function

 Titrate drug dosage with patient response Establish reasonable therapeutic end points Adjust dosage until end points are reached or side effects prevent further increase Use adequate dose : important in the treatment of pain associated with malignancy Sometimes combination therapy is appropriate and effective Simplify the therapeutic regimen and encourage compliance Try to avoid intermittent schedules Label drug containers clearly Give careful instructions to both patient and a relative or friend Explain why the drug is being prescribed Suggest the use of medication calendar or diary Encourage the return or destruction of old medications Supervision of drug therapy by neighbor, relative, friend, visiting nurse may be desirable Regularly review the treatment plan, and discontinue drugs no longer needed. Remember that drugs may cause new problems or exacerbate chronic problems.